Southernmost Asia Is the Source of Japanese Encephalitis Virus (Genotype 1) Diversity from which the Viruses Disperse and Evolve throughout Asia

Abstract

BackgroundAlthough a previous study predicted that Japanese encephalitis virus (JEV) originated in the Malaysia/Indonesia region, the virus is known to circulate mainly on the Asian continent. However, there are no reported systematic studies that adequately define how JEV then dispersed throughout Asia.Methodology/Principal FindingsIn order to understand the mode of JEV dispersal throughout the entire Asian continent and the factors that determine the dispersal characteristics of JEV, a phylogenetic analysis using Bayesian Markov chain Monte Carlo simulations was conducted on all available JEV E gene sequences in GenBank, plus strains recently isolated in China. Here we demonstrate for the first time that JEV lineages can be divided into four endemic cycles, comprising southern Asia, eastern coastal Asia, western Asia, and central Asia. The isolation places of the viruses in each endemic cycle were geographically independent regardless of years, vectors, and hosts of isolation. Following further analysis, we propose that the southernmost region (Thailand, Vietnam, and Yunnan Province, China) was the source of JEV transmission to the Asian continent following its emergence. Three independent transmission routes from the south to north appear to define subsequent dispersal of JEV. Analysis of JEV population dynamics further supports these concepts.Conclusions/SignificanceThese results and their interpretation provide new insights into our understanding of JEV evolution and dispersal and highlight its potential for introduction into non-endemic areas.

The spatiotemporal distribution of Japanese Encephalitis cases in Yunnan Province, China, from 2007 to 2017

“…Until recently, most of the strains of JEV at the origin of major epidemics in the South, East, and Southeast Asia regions belonged to genotype III [18]. However, a shift in prevalence from JEV genotype III to JEV genotype I has been observed in several Asian countries [19][20][21], although an evolutionary study has demonstrated that three genotypes (I, III, V) were confirmed to be co-circulating in China in both high and low prevalence areas [22]. All JEV strains belong to a single serotype, as evident from an epidemiological observation of the absence of secondary encephalitis [23].…”

A Japanese Encephalitis Virus Genotype 5 Molecular Clone Is Highly Neuropathogenic in a Mouse Model: Impact of the Structural Protein Region on Virulence

“…From the isolation of the prototype strain of JEV in 1935 until recently, most of the circulating strains of JEV belonged to g3 and were at the origin of major epidemics in Southeast Asian countries (5). Recently, a shift in prevalence from JEV g3 to g1 has been observed in several Asian countries (6)(7)(8), while some strains of JEV g5 have been occasionally isolated in China in 2009 (9) and in South Korea in 2010 (10). The JEV g5 prototype strain, strain Muar, was originally isolated in 1952 from an encephalitis patient in Malaysia (11) and was found to be genetically and serologically distinct from other genotypes (12)(13)(14).…”

Modelling the skip-and-resurgence of Japanese encephalitis epidemics in Hong Kong

“…some indirect overseas evidence does exist: (i) JEV genotype 1 (G1) strain since 20 0 0: In Southeast Asia, studies reported that Genotype 3 was predominant during the late 20th century, and then genotype 1 started to replace genotype 3 around 20 0 0 and become dominant thereafter ( Gao et al, 2015;Mackenzie et al, 2004;Pan et al, 2011 ). One genetic study found that the genotype 1 strain was not observed until 2008 in the regions of Mainland China surrounding Hong Kong ( Gao et al, 2013 ). Thus, it is very likely that there is a newly introduced JEV strain from pigs imported from these Mainland Chinese regions ( The Government of Hong Kong, Agriculture, Fisheries and Conservation Department, 2017b ); (ii) JEV genotype 5 (G5) strain: Similar JEV resurgences were observed in South Korea in 1998 and 2010 ( Sunwoo et al, 2016 ).…”

“…Thus, it is very likely that there is a newly introduced JEV strain from pigs imported from these Mainland Chinese regions ( The Government of Hong Kong, Agriculture, Fisheries and Conservation Department, 2017b ); (ii) JEV genotype 5 (G5) strain: Similar JEV resurgences were observed in South Korea in 1998 and 2010 ( Sunwoo et al, 2016 ). The resurgence in 1998 was likely due to the introduction of G1 strain in the mid-1990's ( Gao et al, 2013;Mackenzie et al, 2004 ). The first isolated local G5 strain was reported in 2010 in South Korea, which coincided with the resurgence of JEV in 2010 ( Takhampunya et al, 2011 ), where the average number of annual JEV cases increased approximately six-to eight-fold ( Sunwoo et al, 2016 ).…”